Study Design:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  1. Analyze the influence of diurnal variation of gas exchange within individuals and as one group.
  2. Quantify the stochastic and systematic errors introduced by extrapolating from short recording periods varying in duration and number.


Inclusion Criteria:
  1. Continuous mechanical ventilation (intermittent positive pressure, continuous positive pressure, or intermittent mandatory)
  2. FIO2 of .60 or less
  3. No air leakage (i.e., no cuff or thoracic drain leakage)
  4. 6 hr postanesthesia to exclude influence of NO2
  5. Absence of profuse bleeding
  6. Absence of dialysis
Exclusion Criteria:
  1. Refusal to consent
  2. Not meeting inclusion criteria
Description of Study Protocol:


Steady state - Not defined

Total diurnal values – Summation of all minute values per day

Diurnal variation - the 24-h recording period was divided into eight 3-hour intervals. The mean minute values of VO2 and VCO2 in each interval were calculated and expressed as % of the mean diurnal values of VO2 and VCO2


  • Ht measured? No
  • Wt measured? No
  • Fat-free mass measured? No



  • Monitored heart rate?
  • Body temperature? Yes
  • Medications administered? 6 hr post anesthesia
  • Infection/sepsis? Yes

Resting energy expenditure:

  • IC type: Open-circuit respirometry
  • Equipment of Calibration: self-calibrating
  • Coefficient of variation using std gases: Yes or No
  • Steady state: Not mentioned with exception of machine automatically suppressing measurements if expiratory minute volume of <2 L/mn detected thereby dropping the next 5 min and the last minute before the detected decreased expiration.
  • Fasting length: Ongoing enteral or parenteral nutrition in 39 pt
  • Exercise restrictions XX hr prior to test? NA
  • No. of measures within the measurement period: every minute for 24 hr
  • Were some measures eliminated? Yes, artifacts caused by automatic calibration of gas sensors once every 2 hr and by pt ventilator disconnections; also, if expiratory minute volume of less than 2 L/min the algorithm suppresses all detected periods plus the next 5 and the last minute before the detected artifact
  • Training of measurer? Not mentioned
  • Subject training of measuring process? Not mentioned but expected

Statistical tests:

  • To determine whether each 3-hr interval was significantly different from 100% of the mean diurnal value, analysis of variance was used; In the same way for each interval the mean absolute RQ values were compared.
  • The accuracy for the individual pt was expressed as the absolute value of the percent diffference (APD) between the extrapolated and the real, continuously measured diurnal VO2, VCO2, and RQ. The accuracy of the comparison of the APDS using the Wilcoxon rank-sum test.
  • The 16 investigated extrapolated protocols, the linear correlation b/t continuously measured values and extrapolated values was calculated with the jackknife method.
  • Linear regression analysis was used to identify a best fit for the group of patients by identifying the stochastic error of each sampling protocol and systematic error was quantified by the intercept and slope.



Data Collection Summary:

Outcome(s) and other measures

  1. Measured REE [(VO2, l/min), VCO2 (l/min; ml/kg/min), RQ, ventilation (l/min)].
  2. Severity of illness was quantified by the Simplified Acute Physiology Scoring (SAPS) system
  3. Independent variables of gender, age, type of enteral or parenteral nutrition, mortality, and infection


Blinding used: No

Description of Actual Data Sample:
  • N= 50 ICU patients, aged 15-83 yr
  • Mean 55 + 18 yr
  • N= 40 males; N= 10 females

Body temperature mean: 38.2 + 0.9 C

Infection/sepsis: 29 pt (58%)

Recent major operation <5 days:  22 pt (44%)

Fracture/trauma: 12 pt (24%)

Respiratory distress synd: 10 (20%)

Enteral nutr only: 15 pt (30%)

Parenteral nutr only: 22 pt (44%)

Enter + Parenter: 2 pt (4%)

Hospital mortality: 20 pt (40%)

SAPS (n=49): 14+5 (3-26)
Summary of Results:



Number of measurements

There were four intervals evaluated:

  • 1 interval per day at 12 noon
  • 2 intervals per day at 8 AM and 5 PM
  • 3 intervals per day at 8 AM, 12 NOON, 5 PM
  • 4 intervals per day at midnight, 8 AM, 12 noon and 5 PM


Length of measurements

There were 4 short recording periods:

  1. 5 minute
  2. 15 minute
  3. 30 minute
  4. 60 minute


Steady state – Not defined



  • The mean absolute RQ values were compared with the mean diurnal RQ values
  • There was no statistically significant difference between the average RQ value of any 3-hr interval and the mean diurnal RQ values (.87).



  • Sleep or rest
  • Physical activity
  • Food intake
  • Various times in the day



The 3 hr values of both averaged VO2 and VCO2 values were slightly lower during the night than during the day. At some intervals, the deviation from the mean diurnal values was statistically significant, but at each interval this deviation was smaller than 3%.




For VO2 the accuracy was improved by an increase in duration and by an increase in measurements. The accuracy of one single 5-min measurement was improved substantially by increasing the duration of the recording period to 30 min (i.e., one measurement for 30 min > accuracy than one measurement for 5 min; p<.05)


Measuring twice per day instead of once improved the accuracy significantly (VO2: A2X5 >A1 X 5, p <.005). This effect tended to predominate over that of increased duration in one single recording period (i.e., 2- 5 minute recording periods > one 15-minute period, p<.05). Further increase in number raised the accuracy only slightly.



The accuracy of extrapolated VCO2 values was less dependent on the duration of recording periods; an increase in number led to significantly better results (VCO2: 2 5-minute measures were more accurate than 1-5-min measurement, p<.05)



The accuracy of extrapolation was influenced by number and duration: RQ: 2 5-min measurements were more accurate than 1-5 minute measurement, p<.0005; and, one 30 minute measurement was more accurate than one 5-miute measurement; p <0.01)


The mean coefficient of correlation between the extrapolated and the continuously measured values; for VO2, VCO2 and RQ, r increased with increased duration and number of the recording periods.


The extrapolations of VCO2 tended to be slightly more accurate than the estimates of VO2 with the same extrapolation protocol.

Author Conclusion:
  • We have demonstrated that in critically ill surgical patients, the amplitude of diurnal variation of metabolic gas exchange is only about 3%, nocturnal gas exchange measurements are not necessary to get reliable estimates of 24-hr metabolic gas exchange.
  • In the individual patient, large fluctuations in metabolic gas exchange occur which are spread more or less equally over the day.
  • Metabolic rate fluctuations are induced by the following modulating factors: motor activity (e.g., voluntary movements and respiratory labor), nutrition (e.g., specific dynamic action of food), clinical condition (e.g., fever, sepsis, operations, burns), medication (e.g., beta-blocking agents, morphine, barbiturates, and muscle relaxants), discomfort/pain and diurnal variation (e.g., related to sound, light, ambient temperature, hormonal blood levels and renal function).
  • Previous findings suggest modulating factors may cause considerable fluctuations in metabolic rate, for intrapatient or interpatient comparisons, it is essential to measure strictly under standard conditions. . . For practical reason, TEE is only rarely based on 24-h continuous gas exchange measurements.
  • The slightly better accuracy of VCO2 than that of VO2, when the same extrapolation protocol is used, can be explained by the greater buffering capacity for CO2 changes in comparison with the small O2 gas store. . . Furthermore, to achieve a higher accuracy of metabolic measurements is more effective than an increase in duration of measurements.
  • Measuring more than two 15-min periods a day may be rather cumbersome and time-consuming, and it does not lead to a beneficial increase in extrapolation accuracy.
  • A diurnal variation in metabolic gas exchange can hardly be recognized within this group of critically ill, surgical patients. . . modulating factors can cause sugstantial fluctuations in the metabolic rate of the individual patient. In daily clinical practice, estimation of total diurnal VO2, VCO2, and RQ can be achieved satisfactorily by extrapolation from two 14-min gas exchange recordings during the day.
  • One limitation of our study is [none mentioned].
Funding Source:
Reviewer Comments:


  • Given the publication year of 1988, this was a rigorous study to implement.
  • Use of jackknife coefficient of correlation and quantifying stochastic error by linear regression analysis
  • Research performed throughout a typical day in the critical care unit.


  • Generalizable to critical care patients following a major operation, fracture, trauma, respiratory distress (without air leaks), and receiving enteral or parenteral nutrition.
  • Did not discuss that 40% of patients died in the hospital-were all measurements completed on entire sample?
  • Am unsure importance of discussing the modulating factors when these factors were not ‘controlled for’ in their sample.
  • Did not identify if patient restlessness impacted IC measurement.
  • Small sample size

Important variables on REE measurement accuracy not discussed was steady state and intervening factors such as medications, fever, and if the 11 pt NOT on enteral or parenteral nutrition support were NPO or orally fed..”
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? ???
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) ???
Validity Questions
1. Was the research question clearly stated? ???
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? ???
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? ???
  1.3. Were the target population and setting specified? ???
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? ???
  2.2. Were criteria applied equally to all study groups? ???
  2.3. Were health, demographics, and other characteristics of subjects described? ???
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) ???
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? ???
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) ???
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? ???
4. Was method of handling withdrawals described? ???
  4.1. Were follow-up methods described and the same for all groups? ???
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? ???
5. Was blinding used to prevent introduction of bias? ???
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) ???
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? Yes
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? N/A
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? ???
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? ???
  6.6. Were extra or unplanned treatments described? ???
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? ???
  6.8. In diagnostic study, were details of test administration and replication sufficient? ???
7. Were outcomes clearly defined and the measurements valid and reliable? ???
  7.1. Were primary and secondary endpoints described and relevant to the question? ???
  7.2. Were nutrition measures appropriate to question and outcomes of concern? N/A
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? ???
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? ???
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  7.7. Were the measurements conducted consistently across groups? ???
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? ???
  8.2. Were correct statistical tests used and assumptions of test not violated? ???
  8.3. Were statistics reported with levels of significance and/or confidence intervals? ???
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? ???
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? ???
  8.6. Was clinical significance as well as statistical significance reported? ???
  8.7. If negative findings, was a power calculation reported to address type 2 error? ???
9. Are conclusions supported by results with biases and limitations taken into consideration? ???
  9.1. Is there a discussion of findings? ???
  9.2. Are biases and study limitations identified and discussed? ???
10. Is bias due to study's funding or sponsorship unlikely? ???
  10.1. Were sources of funding and investigators' affiliations described? ???
  10.2. Was the study free from apparent conflict of interest? ???